Selenoprotein SELENOK Enhances the Migration and Phagocytosis of Microglial Cells by Increasing the Cytosolic Free Ca2+ Level Resulted from the Up-Regulation of IP3R

Roles of Selenoproteins in Brain Function and the Potential Mechanism of Selenium in Alzheimer’s Disease

“…A study by Fradejas et al (2011) showed that SELENOS overexpression influenced astrocyte functions and reduced the secretion of proinflammatory cytokines to enhance resistance to ER stress and neuroinflammation. As mentioned in the previous sections, SELENOK promotes the migration and phagocytosis of microglia through the regulation of Ca 2+ flux, and SELENOK is the only reported selenoprotein to have direct regulatory functions in microglia (Meng et al, 2019). SELENOM may reduce the oxidative stress level in cerebellar astrocytes, in addition to neurons, through the regulation of Ca 2+ flux (Reeves et al, 2010).…”

“…To date, no evidence indicates that SELENOS is directly involved in Ca 2+ regulation. However, studies have shown that SELENOK can interact with a palmitoyltransferase (DHHC6) to affect Ca 2+ flux through regulation of inositol 1, 4, 5-trisphosphate receptor (IP3R) palmitoylation (Verma et al, 2011;Fredericks et al, 2014) and that SELENOK overexpression increases IP3R-mediated free Ca 2+ levels in microglia (Meng et al, 2019). Furthermore, a cyclic adenosine monophosphate (cAMP)-mediated increase in Ca 2+ levels in neuronal cells was shown to significantly improve SELENOT expression.…”

“…The interaction between SELENOK and DHHC6 effectively catalyzes the palmitoylation of proteins such as IP3R and CD36 to stabilize their expression and further promote Ca 2+ flux in the ER to activate immune cells (Fredericks et al, 2014;Fredericks and Hoffmann, 2015;Marciel and Hoffmann, 2019). Microglia-mediated neuroinflammation is considered a major AD-inducing factor (Tejera and Heneka, 2016;Hansen et al, 2018), and SELENOK overexpression significantly increases the Ca 2+ level and IP3R expression and promotes the migration and phagocytosis of microglia to regulate neuroimmunity and neuroinflammation in the brain (Meng et al, 2019). However, the direct relationship between SELENOK and AD has not been reported until recently.…”

Phagocytosis of full-length Tau oligomers by Actin-remodeling of activated microglia

“…Significant at the mean difference between treatment groups (X − X`) > Tukey's criterion (T) secretion of different cytokines and chemokines, attracting neighboring microglia to speed up the process of the active clearance of deposited misfolded proteins and degenerated neuronal bodies [61]. Intracellular calcium level plays an important role in microglial migration activation [62], and a calcium-dependent adaptor protein, Iba1, was found to be upregulated by the overexpression of hTau40 in microglia [63]. It was reported that the IFN-γ, IL-1β, and tissue injury could increase the Iba1 levels related to cellular proliferation and migration [64].…”

Bisbenzylisoquinoline alkaloids of lotus ( Nelumbo nucifera Gaertn.) seed embryo inhibit lipopolysaccharide-induced macrophage activation via suppression of Ca 2+ -CaM/CaMKII pathway

“…The level of cytosolic free Ca 2+ was also monitored using the Fura-2/AM fluorescent indicator as previously described (Meng et al, 2019). Briefly, the treated cells were washed twice with D-Hanks and loaded with 5 μM of Fura-2/AM (Sigma) at 37°C for 60 min in dark.…”